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commentary on some recent theses relevant to combating aging: october 2019.theses reviewed in this issue include "cancer and stem cell extravasation through angiopellosis," "human chimeric antigen receptor macrophages for cancer immunotherapy," "insights on alzheimer's disease etiology from network approaches in healthy aging," "myelin and glial pathology in aging and cognitive decline: evidence for faulty myelin clearance in the rhesus monkey," "phosphatidylserine-based nanoparticles for tolerance induction toward therapeutic proteins," and "role of endothelial cell s ...201931571532
bcl6 btb-specific inhibition via fx1 treatment reduces tfh cells and reverses lymphoid follicle hyperplasia in indian rhesus macaque (macaca mulatta).the btb domain of b-cell lymphoma 6 (bcl6) protein was identified as a therapeutic target for b-cell lymphoma. this study compared the pharmacokinetics (pk) of the bcl6 btb inhibitor (fx1) between mice and macaques, as well as evaluating its lymphoid suppressive effect in uninfected macaques with lymphoid hyperplasia.202031571234
social hair plucking is a grooming convention in a group of captive bonobos (pan paniscus).hair plucking is observed in many captive primate species and is often characterized as an abnormal behavior. however, this behavior may be both self-directed and social and may have different etiologies. early research in captive macaques (macaca mulatta) described the aggressive nature of social hair plucking while more recent observations did not find an association with aggression or grooming, but the behavior was initiated most frequently by individuals with more secure dominance rank. here ...201931571101
influence of cranial irradiation with high-energy protons on the visuomotor behavior in monkeys.the visually driven instrumental conditioning of a single monkey (macaca mulatta) was conducted after single-dose cranial irradiation with high-energy protons. the monkey executed saccades toward the visual stimuli and then responded by manually pressing right or left lever for stimuli in right or left half-field, respectively. the percentage of correct responses with dominant right hand exceeded the percentage of such responses with left hand and temporarily decreased two months after irradiati ...201931571073
vaccine protection against rectal acquisition of sivmac239 in rhesus macaques.a prophylactic vaccine against human immunodeficiency virus (hiv) remains a top priority in biomedical research. given the failure of conventional immunization protocols to confer robust protection against hiv, new and unconventional approaches may be needed to generate protective anti-hiv immunity. here we vaccinated rhesus macaques (rms) with a recombinant (r)dna prime (without any exogenous adjuvant), followed by a booster with rhesus monkey rhadinovirus (rrv)-a herpesvirus that establishes p ...201931568531
do young rhesus macaques know what others see?: a comparative developmental perspective.humans undergo robust ontogenetic shifts in the theory of mind capabilities. are these developmental changes unique to human development or are they shared with other closely related non-human species? to explore this issue, we tested the development of the theory of mind capacities in a population of 236 infant and juvenile rhesus macaques (macaca mulatta). using a looking-time method, we examined what developing monkeys know about others' perceptions. specifically, we tested whether younger mo ...202031566777
long-term survival of full-thickness corneal xenografts from α1,3-galactosyltransferase gene-knockout miniature pigs in non-human primates.we aimed to investigate (a) the long-term survival of corneal grafts from α1,3-galactosyltransferase gene-knockout miniature (gtkom) pigs in non-human primates as a primary outcome and (b) the effect of anti-cd20 antibody on the survival of corneal grafts from gtkom pigs as a secondary outcome.202031566261
recombinant human interleukin-15 and anti-pd-l1 combination therapy expands a cxcr3+pd1-/low cd8 t-cell subset in simian immunodeficiency virus-infected rhesus macaques.the pd1/pd-l1 pathway contributes to the pathogenesis of human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) infection, and blockade of this pathway may have potential to restore immune function and promote viral control or elimination. in this study, we combined a checkpoint inhibitor anti-pd-l1 (avelumab) and recombinant human interleukin-15 (rhil-15) in siv-infected rhesus macaques (rm).202031562760
total-body pet and highly stable chelators together enable meaningful 89zr-antibody pet studies up to 30 days after injection.the use of 89zr-antibody pet imaging to measure antibody biodistribution and tissue pharmacokinetics is well established, but current pet systems lack the sensitivity needed to study 89zr-labeled antibodies beyond 2-3 isotope half-lives (7-10 d), after which a poor signal-to-noise ratio is problematic. however, studies across many weeks are desirable to better match antibody circulation half-life in human and nonhuman primates. these studies investigated the technical feasibility of using the pr ...202031562219
reply to "a comment on 'current status of hepatitis e virus infection at a rhesus monkey farm in china'". 201931561923
voluntary chronic heavy alcohol consumption in male rhesus macaques suppresses cancellous bone formation and increases bone marrow adiposity.chronic heavy alcohol consumption is an established risk factor for bone fracture, but comorbidities associated with alcohol intake may contribute to increased fracture rates in alcohol abusers. to address the specific effects of alcohol on bone, we used a nonhuman primate model and evaluated voluntary alcohol consumption on: (i) global markers of bone turnover in blood and (ii) cancellous bone mass, density, microarchitecture, turnover, and microdamage in lumbar vertebra.201931557335
culture model for non-human primate choroid plexus.while there are murine and rat choroid plexus epithelial cell cultures, a translationally relevant model for choroid plexus activation and function is still lacking. the rhesus macaque is the gold standard for modeling viral infection and activation of cns, including hiv-associated neurocognitive disorders. we have developed a rhesus macaque choroid plexus epithelial cell culture model which we believe to be suitable for studies of inflammation associated with viral infection of the cns. epithel ...201931555096
differential effect of mucosal nkp44+ innate lymphoid cells and δγ cells on simian immunodeficiency virus infection outcome in rhesus macaques.nk cells are essential for controlling viral infections. we investigated nk cell and innate lymphoid cell (ilc) dynamics and function in rhesus macaque rectal tissue and blood following mucosal priming with replicating adenovirus (ad)-siv recombinants, systemic boosting with siv envelope protein, and subsequent repeated low-dose intravaginal siv exposures. mucosal memory-like nk and ilc subsets in rectal and vaginal tissues of chronically infected macaques were also evaluated. no differences in ...201931554692
novel primate bocaparvovirus species 3 identified in wild macaca mulatta in china.primate bocaparvovirus (bov) is a possible cause of respiratory disorders and gastroenteritis in humans. however, the diversity and evolution of these viruses remain largely unknown, despite the identification of a growing number of bovs in non-human primates (nhps). here, we report the identification of a novel bov (provisionally named macaca mulatta bocaparvovirus [mmbov]) in the feces of wild macaca mulatta in china by viral metagenomic analysis. seven of 400 fecal samples from macaca mulatta ...202031552610
reduction of peak viremia by an integration-defective siv proviral dna vaccine in rhesus macaques.an integrase-defective siv (idsiv) vaccine delivered by a dna prime and viral particle boost approach can suppress viral loads (vls) during the acute infection stage after intravenous sivmac239 challenge. this study investigated how idsiv dna and viral particle immunization alone contributed to the suppression of vls in chinese rhesus macaques after siv challenge. two macaques were immunized with idsiv dna five times and two macaques were immunized with idsiv viral particles three times. cellula ...202031544982
the association of iron and the pathologies of parkinson's diseases in mptp/mpp+-induced neuronal degeneration in non-human primates and in cell culture.despite much efforts in the last few decades, the mechanism of degeneration of dopamine (da) neurons in the substantia nigra (sn) in parkinson's disease (pd) remains unclear. this represents a major knowledge gap in idiopathic and genetic forms of pd. among various possible key factors postulated, iron metabolism has been widely suggested to be involved with fueling oxidative stress, a known factor in the pathogenesis of pd. however, the correlation between iron and da neuron loss, specifically ...201931543809
a comment on "current status of hepatitis e virus infection at a rhesus monkey farm in china". 201931543286
the relationship between the uncinate fasciculus and anxious temperament is evolutionarily conserved and sexually dimorphic.anxious temperament (at) is an early-life heritable trait that predisposes individuals to develop anxiety and depressive disorders. our previous work in preadolescent children suggests alterations in the uncinate fasciculus (uf), the white matter tract that connects prefrontal with limbic regions, in boys with anxiety disorders. here, using a nonhuman primate model of at, we tested whether this sexually dimorphic finding is evolutionarily conserved and examined the extent to which heritable and ...201931542153
chemogenetic inhibition of the amygdala modulates emotional behavior expression in infant rhesus monkeys.manipulation of neuronal activity during the early postnatal period in monkeys has been largely limited to permanent lesion studies, which can be impacted by developmental plasticity leading to reorganization and compensation from other brain structures that can interfere with the interpretations of results. chemogenetic tools, such as dreadds (designer receptors exclusively activated by designer drugs), can transiently and reversibly activate or inactivate brain structures, avoiding the pitfall ...202031541000
humoral immunity prevents clinical malaria during plasmodium relapses without eliminating gametocytes.plasmodium relapses are attributed to the activation of dormant liver-stage parasites and are responsible for a significant number of recurring malaria blood-stage infections. while characteristic of human infections caused by p. vivax and p. ovale, their relative contribution to malaria disease burden and transmission remains poorly understood. this is largely because it is difficult to identify 'bona fide' relapse infections due to ongoing transmission in most endemic areas. here, we use the p ...201931536608
oral dosing for antenatal corticosteroids in the rhesus macaque.antenatal corticosteroids (acs) are standard of care for women at risk of preterm delivery, although choice of drug, dose or route have not been systematically evaluated. further, acs are infrequently used in low resource environments where most of the mortality from prematurity occurs. we report proof of principle experiments to test betamethasone-phosphate (beta-p) or dexamethasone-phosphate (dex-p) given orally in comparison to the clinical treatment with the intramuscular combination drug be ...201931536601
neonatal temperament and neuromotor differences are predictive of adolescent alcohol intake in rhesus monkeys (macaca mulatta).identifying predictors of teenage alcohol use disorder (auds) is a major health initiative, with studies suggesting that there are distinct personality-related traits that underlie patterns of alcohol intake. as temperament is biologically based, identifiable early in life, and stable across time, it is considered the foundation of personality. as such, we hypothesized that neonatal temperament traits would predict anxiety-mediated adolescent alcohol consumption. to test this, n = 145 rhesus mac ...202031536163
multidimensional neural selectivity in the primate amygdala.the amygdala contributes to multiple functions including attention allocation, sensory processing, decision-making, and the elaboration of emotional behaviors. the diversity of functions attributed to the amygdala is reflected in the response selectivity of its component neurons. previous work claimed that subsets of neurons differentiate between broad categories of stimuli (e.g., objects vs faces, rewards vs punishment), while other subsets are narrowly specialized to respond to individual face ...202031533960
effects of 7-methylxanthine on deprivation myopia and retinal dopamine release in chickens.intake of 7-methylxanthine (7-mx), an adenosine receptor (ar) antagonist, has been shown to inhibit school myopia in children and deprivation myopia in rhesus monkeys, but the underlying mechanisms are not known. also retinal dopamine seems to be involved in the control of eye growth, and in the brain, ars and dopamine receptors interact widely by heteromerization. we have studied whether 7-mx can inhibit deprivation myopia also in chickens and whether inhibition may involve the retinal dopamine ...202031533122
eye-head-hand coordination during visually guided reaches in head-unrestrained macaques.nonhuman primates have been used extensively to study eye-head coordination and eye-hand coordination, but the combination-eye-head-hand coordination-has not been studied. our goal was to determine whether reaching influences eye-head coordination (and vice versa) in rhesus macaques. eye, head, and hand motion were recorded in two animals with search coil and touch screen technology, respectively. animals were seated in a customized "chair" that allowed unencumbered head motion and reaching in d ...201931533015
impacts of early social experience on cognitive development in infant rhesus macaques.although much is known about the influences of early life experiences on the neurobiology and behavior of macaque models of child development, there is scant literature on cognitive development with respect to early rearing. here, we examined the effects of rearing condition on affective reactivity and cognitive development in infant rhesus macaques. infants were pseudo-randomly assigned to one of the two rearing conditions: nursery reared (nr, n = 32; 16 peer-reared, 16 surrogate-peer-reared) o ...202031531855
long-read assembly of the chinese rhesus macaque genome and identification of ape-specific structural variants.we present a high-quality de novo genome assembly (rhemacs) of the chinese rhesus macaque (macaca mulatta) using long-read sequencing and multiplatform scaffolding approaches. compared to the current indian rhesus macaque reference genome (rhemac8), rhemacs increases sequence contiguity 75-fold, closing 21,940 of the remaining assembly gaps (60.8 mbp). we improve gene annotation by generating more than two million full-length transcripts from ten different tissues by long-read rna sequencing. we ...201931530812
effect of anesthesia on intraocular pressure measured with continuous wireless telemetry in nonhuman primates.to compare the effects of both injectable anesthesia (ketamine/dexmedetomidine versus ketamine/xylazine) and inhalant anesthesia (isoflurane) on iop using continuous, bilateral iop telemetry in nonhuman primates (nhp).201931529079
hematological and biochemical parameters for chinese rhesus macaque.rhesus macaque is an important animal model in biomedical research, especially human disease, developmental, translational, and pre-clinical research. blood physiological and biochemical parameters are important markers for physiology, pathology, and toxicology research. however, these parameters have not been systematically reported for chinese rhesus macaques. to characterize the reference for these parameters, this study collected 1805 chinese rhesus macaques living in southwestern china. a t ...201931527891
social touch alters newborn monkey behavior.in humans, infants respond positively to slow, gentle stroking-processed by c-tactile (ct) nerve fibers-by showing reductions in stress and increases in eye contact, smiling, and positive vocalizations. more frequent maternal touch is linked to greater activity and connectivity strength in social brain regions, and increases children's attention to and learning of faces. it has been theorized that touch may prime children for social interactions and set them on a path towards healthy social cogn ...201931521911
impact of intensive care unit supportive care on the physiology of ebola virus disease in a universally lethal non-human primate model.there are currently limited data for the use of specific antiviral therapies for the treatment of ebola virus disease (evd). while there is anecdotal evidence that supportive care may be effective, there is a paucity of direct experimental data to demonstrate a role for supportive care in evd. we studied the impact of icu-level supportive care interventions including fluid resuscitation, vasoactive medications, blood transfusion, hydrocortisone, and ventilator support on the pathophysiology of e ...201931520194
capuchin and rhesus monkeys but not humans show cognitive flexibility in an optional-switch task.learned rules help us accurately solve many problems, but by blindly following a strategy, we sometimes fail to find more efficient alternatives. previous research found that humans are more susceptible to this "cognitive set" bias than other primates in a nonverbal computer task. we modified the task to test one hypothesis for this difference, that working memory influences the advantage of taking a shortcut. during training, 60 humans, 7 rhesus macaques, and 22 capuchin monkeys learned to sele ...201931519948
digit ratio (2d:4d) and its behavioral correlates in infant rhesus macaques (macaca mulatta).2d:4d ratios are typically lower in adult human males than females and are linked to numerous sex-differentiated behaviors. 2d:4d ratios are considered an indicator of prenatal androgen exposure; if so, children's 2d:4d ratios would arguably be even better indicators of prenatal androgen exposure since children have experienced fewer postnatal influences than adults. however, sex differences in 2d:4d ratios as well as associations between 2d:4d ratios and sex-typed behaviors in children have bee ...202031512755
[features of endocrine function of the pancreas with aging in nonhuman primates with various types of adaptive behavior.]an increasing number of studies are devoted to the study of the relationship of mental disorders, such as depression and anxiety, with the risk of developing type 2 diabetes mellitus. however, in the literature there are practically no publications on the study of the relationship of the features of higher nervous activity, in particular, adaptive behavior, in healthy individuals with the risk of developing age-related dysfunction of the pancreatic islet apparatus (pia). the purpose of this stud ...201931512416
impact of ferumoxytol magnetic resonance imaging on the rhesus macaque maternal-fetal interface†.ferumoxytol is a superparamagnetic iron oxide nanoparticle used off-label as an intravascular magnetic resonance imaging (mri) contrast agent. additionally, ferumoxytol-uptake by macrophages facilitates detection of inflammatory sites by mri through ferumoxytol-induced image contrast changes. therefore, ferumoxytol-enhanced mri holds great potential for assessing vascular function and inflammatory response, critical to determine placental health in pregnancy. this study sought to assess the feto ...202031511859
rhesus macaques use probabilities to predict future events.humans can use an intuitive sense of statistics to make predictions about uncertain future events, a cognitive skill that underpins logical and mathematical reasoning. recent research shows that some of these abilities for statistical inferences can emerge in preverbal infants and non-human primates such as apes and capuchins. an important question is therefore whether animals share the full complement of intuitive reasoning abilities demonstrated by humans, as well as what evolutionary contexts ...201931511761
glissades are altered by lesions to the oculomotor vermis but not by saccadic adaptation.saccadic eye movements enable fast and precise scanning of the visual field, which is partially controlled by the posterior cerebellar vermis. textbook saccades have a straight trajectory and a unimodal velocity profile, and hence have well-defined epochs of start and end. however, in practice only a fraction of saccades matches this description. one way in which a saccade can deviate from its trajectory is the presence of an overshoot or undershoot at the end of a saccadic eye movement just bef ...201931507389
flexible combination of reward information across primates.a fundamental but rarely contested assumption in economics and neuroeconomics is that decision-makers compute subjective values of risky options by multiplying functions of reward probability and magnitude. by contrast, an additive strategy for valuation allows flexible combination of reward information required in uncertain or changing environments. we hypothesized that the level of uncertainty in the reward environment should determine the strategy used for valuation and choice. to test this h ...201931501543
systematic evaluation of suspension mdck cells, adherent mdck cells, and llc-mk2 cells for preparing influenza vaccine seed virus.suspension madin-darby canine kidney (mdck) cells (mdck-n), adherent mdck cells (mdck-c), and adherent rhesus monkey kidney llc-mk2 cells (llc-mk2d) were systematically evaluated for the preparation of influenza vaccine seed viruses for humans on the basis of primary virus isolation efficiency, growth ability, genetic stability of the hemagglutinin (ha) and neuraminidase (na) genes, and antigenic properties in hemagglutination inhibition (hi) test of each virus isolate upon further passages. all ...201931500967
in utero androgen excess: a developmental commonality preceding polycystic ovary syndrome?in utero androgen excess reliably induces polycystic ovary syndrome (pcos)-like reproductive and metabolic traits in female monkeys, sheep, rats, and mice. in humans, however, substantial technical and ethical constraints on fetal sampling have curtailed safe, pathogenic exploration during gestation. evidence consistent with in utero origins for pcos in humans has thus been slow to amass, but the balance now leans toward developmental fetal origins. given that pcos is familial and highly heritab ...201931499494
construction of a comprehensive observer-based scale assessing aging-related health and functioning in captive rhesus macaques.aging-related health and functioning are difficult to quantify in humans and nonhuman primates. we constructed an observer-based scale for daily application in assessing the aging-related health and functioning of rhesus macaques. ten items referring to an aging appearance, musculoskeletal aging and aging-related eating behavior were selected through a panel consensus. the aging-related health and functioning scale (ahfs) was constructed based on these scored items form 57 healthy rhesus macaque ...201931498777
increased cd68/tgfβ co-expressing microglia/ macrophages after transient middle cerebral artery occlusion in rhesus monkeys.the function of microglia/macrophages after ischemic stroke is poorly understood. this study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (mcao) in rhesus monkeys. we measured infarct volume and neurological function by magnetic resonance imaging (mri) and non-human primate stroke scale (nhpss), respectively, to assess temporal changes following mcao. activated phagocytic microglia/macrophages were examined by immunohistoch ...201931495075
formation of alcohol motivation in monkeys (macaca mulatta) kept in isolation.the effects of environmental factors (flavors, different ethanol concentration, alcoholic deprivation, and food reinforcement) on the formation of alcohol motivation was studied in rhesus macaques (macaca mulatta, n=6). motivation for alcohol intake was induced in two stages: initiation (sessions 1-160) and formation of motivation (sessions 161-516). monkeys preferred multifruit flavor and 4% ethanol solution, while ethanol deprivation did not stimulate alcohol consumption. the pronounced indivi ...201931494767
a population stereotaxic positron emission tomography brain template for the macaque and its application to ischemic model.positron emission tomography (pet) is a non-invasive imaging tool for the evaluation of brain function and neuronal activity in normal and diseased conditions with high sensitivity. the macaque monkey serves as a valuable model system in the field of translational medicine, for its phylogenetic proximity to man. to translation of non-human primate neuro-pet studies, an effective and objective data analysis platform for neuro-pet studies is needed.201931494249
gender differences in innate responses and gene expression profiles in memory cd4 t cells are apparent very early during acute simian immunodeficiency virus infection.gender differences in human immunodeficiency virus (hiv) disease progression and comorbidities have been extensively reported. using the simian immunodeficiency virus (siv) infected rhesus macaque model, we show that these differences are apparent very early during the course of infection. though there were no major changes in the proportions of cd4 t cells or its subsets, central memory cd4 t cells from female macaques were found to differentially regulate a significantly larger number of genes ...201931490965
blocking α4β7 integrin binding to siv does not improve virologic control.a study in nonhuman primates reported that infusions of an antibody against α4β7 integrin, in combination with antiretroviral therapy, showed consistent, durable control of simian immunodeficiency virus (siv) in rhesus macaques. the antibody used has pleiotropic effects, so we set out to gain insight into the underlying mechanism by comparing this treatment to treatment with non-neutralizing monoclonal antibodies against the siv envelope glycoprotein that only block α4β7 binding to siv env but h ...201931488690
lack of therapeutic efficacy of an antibody to α4β7 in sivmac251-infected rhesus macaques.sustained virologic control of human immunodeficiency virus type 1 (hiv-1) infection after discontinuation of antiretroviral therapy (art) is a major goal of the hiv-1 cure field. a recent study reported that administration of an antibody against α4β7 induced durable virologic control after art discontinuation in 100% of rhesus macaques infected with an attenuated strain of simian immunodeficiency virus (siv) containing a stop codon in nef we performed similar studies in 50 rhesus macaques infec ...201931488689
evaluation of an antibody to α4β7 in the control of sivmac239-nef-stop infection.treatment of siv-infected rhesus macaques with short-term antiretroviral therapy (art) and partially overlapping infusions of antibody to integrin α4β7 was reported to induce durable posttreatment viral suppression. in an attempt to replicate those observations, we treated macaques infected with the same virus and with the same art and monoclonal antibody (mab) regimens (anti-α4β7 versus control mab). sequencing demonstrated that the virus used was actually sivmac239-nef-stop, not wild-type sivm ...201931488688
analytical treatment interruption after short-term antiretroviral therapy in a postnatally simian-human immunodeficiency virus-infected infant rhesus macaque model.to achieve long-term viral remission in human immunodeficiency virus (hiv)-infected children, novel strategies beyond early antiretroviral therapy (art) will be necessary. identifying clinical predictors of the time to viral rebound upon art interruption will streamline the development of novel therapeutic strategies and accelerate their evaluation in clinical trials. however, identification of these biomarkers is logistically challenging in infants, due to sampling limitations and the potential ...201931488511
intestinal proteomic analysis of a novel non-human primate model of experimental colitis reveals signatures of mitochondrial and metabolic dysfunction.animal models recapitulating features of chronic colitis, such as ulcerative colitis, crohn's disease, or hiv infection, are critical to study disease pathogenesis and test novel therapeutics. in this study, we used a proteomics approach to explore the molecular intestinal response in two rhesus macaque (rm) animal models of experimentally induced colitis using dextran sulfate sodium (dss) and simian immunodeficiency virus (siv) infection. proteomic analysis detected more than 2500 proteins in c ...201931481749
in vitro responses of multiple cytokines to purified protein derivative in healthy and naturally mycobacterium tuberculosis-infected rhesus monkeys (macaca mulatta).as the widely used biomarker of whole-blood stimulation assays for tuberculosis diagnosis, the release of ifn-γ might be affected by multiple factors, such as immunosuppression and some infectious agents. here, we evaluated additional cytokines as diagnostic biomarkers.201931478213
engineering of a lectibody targeting high-mannose-type glycans of the hiv envelope.high-mannose-type glycans (hmgs) are aberrantly enriched on hiv envelope glycoproteins. however, there is currently no drug selectively targeting hiv-associated hmgs. here, we describe a novel hmg-targeting "lectibody," a recombinant fc-fusion protein comprising human igg1 fc and a novel actinohivin lectin variant (avaren) obtained by structure-guided modifications for improved overall surface charge properties (avfc). avfc was engineered and produced using a rapid and scalable plant-based trans ...201931471224
serotonin transporter binding potentials in brain of juvenile monkeys 1 year after discontinuation of a 2-year treatment with fluoxetine.the potential long-term effects of childhood fluoxetine therapy on brain serotonin systems were studied using a nonhuman primate model, the rhesus monkey.201931471184
steroid hormone concentrations in milk predict sex-specific offspring growth in a nonhuman primate.in humans and other mammals, maternal hormones are transferred to offspring during lactation via milk and may regulate postnatal development, including the pace of early growth. here, we used a nonhuman primate model to test the hypotheses that milk cortisol and dehydroepiandrosterone-sulfate (dheas) concentrations reflect maternal characteristics, and that changes in these hormones across lactation are associated with early postnatal growth rates.201931468643
antimicrobial peptide road-1 triggers phase change in local membrane environment to execute its activity.emergence of antibiotic-resistant pathogens has paved way for development of newer class of drugs that would not be susceptible to resistance. antimicrobial peptides such as defensins that target the microbial membrane are promising candidates. road-1 is an alpha-defensin present in the oral cavity of rhesus macaque and shares very high sequence similarity to human enteric defensin 5. in this study we have performed microsecond long all atom molecular dynamic simulations to understand the mechan ...201931468141
population response magnitude variation in inferotemporal cortex predicts image memorability.most accounts of image and object encoding in inferotemporal cortex (it) focus on the distinct patterns of spikes that different images evoke across the it population. by analyzing data collected from it as monkeys performed a visual memory task, we demonstrate that variation in a complementary coding scheme, the magnitude of the population response, can largely account for how well images will be remembered. to investigate the origin of it image memorability modulation, we probed convolutional ...201931464687
opioid-enhancing antinociceptive effects of delta-9-tetrahydrocannabinol and amitriptyline in rhesus macaques.cannabinoids can enhance the antinociceptive effects of opioids in a synergistic manner, potentially reducing the analgesic dosage of opioids and improving pain therapy. this strategy has also been used as a rationale to combine certain antidepressants and opioids. in this experiment, opioid-induced thermal antinociception was assessed in rhesus macaques using a warm-water tail-withdrawal procedure with 3 water temperatures (40, 50, and 55 °c). in general, the acute antinociceptive effects of in ...201931464475
acute transient tachypnea following gadoxetate administration in a rhesus macaque during contrast-enhanced magnetic resonance imaging.during an infectious disease modeling study, a rhesus macaque (macaca mulatta), experienced acute transient tachypnea including transient severe motion during the 70-second phases of serial contrast-enhanced magnetic resonance imaging of the abdomen. this same animal experienced transient severe motion during all but 2 of the 8 scans of the year-long study. this animal was the only animal in the study (1 of 12) to have this reaction to gadoxetate; the animal also vomited after the contrast injec ...201931462952
orbitofrontal cortex is selectively activated in a primate model of attentional bias to cocaine cues.attentional bias to drug-associated cues correlates with extent of current use, and risk of relapse among those attempting abstinence. electroencephalogram (eeg) and functional imaging measures in clinical studies have previously investigated the neural basis of attentional bias, but the lack of animal models precluded investigation at the single-unit level. to complement results obtained from clinical studies, we have employed a non-human primate model of attentional bias to cocaine cues while ...202031461747
cross-species co-analysis of prefrontal cortex chronic ethanol transcriptome responses in mice and monkeys.despite recent extensive genomic and genetic studies on behavioral responses to ethanol, relatively few new therapeutic targets for the treatment of alcohol use disorder have been validated. here, we describe a cross-species genomic approach focused on identifying gene networks associated with chronic ethanol consumption. to identify brain mechanisms underlying a chronic ethanol consumption phenotype highly relevant to human alcohol use disorder, and to elucidate potential future therapeutic tar ...201931456662
maturation of the infant rhesus macaque gut microbiome and its role in the development of diarrheal disease.diarrhea is the second leading cause of death in children under 5 years of age. enhanced understanding of causal pathways, pathogenesis, and sequelae of diarrhea is urgently needed. although the gut microbiota is believed to play a role in susceptibility to diarrheal diseases, our understanding of this association remains incomplete. infant rhesus macaques (macaca mulatta) are susceptible to diarrhea making them an ideal model to address this question.201931451108
50 years ago in the journal ofpediatrics: the effect of pentobarbital anesthesia on resuscitation and brain damage in fetal rhesus monkeys asphyxiated on delivery. 201931439171
a high-quality genome assembly for the endangered golden snub-nosed monkey (rhinopithecus roxellana).the golden snub-nosed monkey (rhinopithecus roxellana) is an endangered colobine species endemic to china, which has several distinct traits including a unique social structure. although a genome assembly for r. roxellana is available, it is incomplete and fragmented because it was constructed using short-read sequencing technology. thus, important information such as genome structural variation and repeat sequences may be absent.201931437279
repeated semen exposure decreases cervicovaginal sivmac251 infection in rhesus macaques.semen is the vehicle for virion dissemination in the female reproductive tract (frt) in male-to-female hiv transmission. recent data suggests that higher frequency semen exposure is associated with activation of anti-hiv mechanisms in hiv negative sex workers. here, we use a non-human primate (nhp) model to show that repeated vaginal exposure to semen significantly reduces subsequent infection by repeated low-dose vaginal sivmac251 challenge. repeated semen exposures result in lower ccr5 express ...201931434895
preferential small intestine homing and persistence of cd8 t cells in rhesus macaques achieved by molecularly engineered expression of ccr9 and reduced ex vivo manipulation.adoptive cell transfer (act) is a powerful experimental approach to directly study t-cell-mediated immunity in vivo in the rhesus macaque aids virus model, infusing simian immunodeficiency virus (siv)-infected animals with cd8 t cells engineered to express anti-siv t-cell receptor specificities enables direct experimentation to better understand antiviral t-cell immunity in vivo limiting factors in act experiments include suboptimal trafficking to, and poor persistence in, the secondary lymphoid ...201931434738
multineuromodulator measurements across fronto-striatal network areas of the behaving macaque using solid-phase microextraction.different neuromodulators rarely act independent from each other to modify neural processes but are instead coreleased, gated, or modulated. to understand this interdependence of neuromodulators and their collective influence on local circuits during different brain states, it is necessary to reliably extract local concentrations of multiple neuromodulators in vivo. here we describe results using solid-phase microextraction (spme), a method providing sensitive, multineuromodulator measurements. ...201931433731
dexamethasone provides effective immunosuppression for improved survival of retinal organoids after epiretinal transplantation.we investigated the efficacy of the immunosuppressants rapamycin (rap) and dexamethasone (dex) in improving the survival of retinal organoids after epiretinal transplantation. we first compared the immunosuppressive abilities of dex and rap in activated microglia in an in vitro setting. following this, we used immunofluorescence, real-time polymerase chain reaction, and flow cytometry to investigate the effects of dex and rap on cells in the retinal organoids. retinal organoids were then seeded ...201931428159
the altered gut virome community in rhesus monkeys is correlated with the gut bacterial microbiome and associated metabolites.the gut microbiome is closely associated with the health of the host; although the interaction between the bacterial microbiome and the whole virome has rarely been studied, it is likely of medical importance. examination of the interactions between the gut bacterial microbiome and virome of rhesus monkey would significantly contribute to revealing the gut microbiome composition.201931426820
cerebral cysts of ependymal or ventricular origin in a juvenile rhesus macaque (macaca mulatta) with neurologic signs.naturally occurring neurologic disease in non-human primates may be attributable to a wide-range of causes, including infectious agents, congenital or acquired malformations, degenerative diseases, and, rarely, neoplasia. we report a case of ataxia and paresis in a juvenile rhesus macaque with ependymal-lined cerebral cysts.201931424092
dorsal amygdala neurotrophin-3 decreases anxious temperament in primates.an early-life anxious temperament (at) is a risk factor for the development of anxiety, depression, and comorbid substance abuse. we validated a nonhuman primate model of early-life at and identified the dorsal amygdala as a core component of at's neural circuit. here, we combine rna sequencing, viral-vector gene manipulation, functional brain imaging, and behavioral phenotyping to uncover at's molecular substrates.201931422797
group i metabotropic glutamate receptors in the primate motor thalamus: subsynaptic association with cortical and sub-cortical glutamatergic afferents.preclinical evidence indicates that mglur5 is a potential therapeutic target for parkinson's disease and l-dopa-induced dyskinesia. however, the mechanisms through which these therapeutic benefits are mediated remain poorly understood. although the regulatory role of mglur5 on glutamatergic transmission has been examined in various basal ganglia nuclei, very little is known about the localization and function of mglur5 in the ventral motor and intralaminar thalamic nuclei, the main targets of ba ...201931422483
metabolism and disposition of arsenic species from controlled dosing with sodium arsenite in adult and neonatal rhesus monkeys. vi. toxicokinetic studies following oral administration.arsenic is a common toxic contaminant in food and drinking water. metabolic activation of arsenic species produces reactive trivalent intermediates that can disrupt cellular regulatory systems by covalent binding to thiol groups. arsenic exposures have been associated with human diseases including cancer, diabetes, lung and cardiovascular disorders and there is accumulating evidence that early life exposures are important in the etiology. previous toxicokinetic studies of arsenite ingestion in n ...201931421213
aav-php.b administration results in a differential pattern of cns biodistribution in non-human primates compared with mice.the ability of recombinant adeno-associated virus (aav) to deliver transgenes to the cns has allowed for several advancements in the field of gene therapy to treat brain disorders. although most aavs do not readily cross the blood-brain barrier and transduce the cns following peripheral administration, aav-php.b has recently been shown to transduce brains of mice with higher efficiency compared with its parent serotype, aav9, following injection into the retro-orbital sinus. here, we extended th ...201931420242
viral-mediated optogenetic stimulation of peripheral motor nerves in non-human primates.objective: reanimation of muscles paralyzed by disease states such as spinal cord injury remains a highly sought therapeutic goal of neuroprosthetic research. optogenetic stimulation of peripheral motor nerves expressing light-sensitive opsins is a promising approach to muscle reanimation that may overcome several drawbacks of traditional methods such as functional electrical stimulation (fes). however, the utility of these methods has only been demonstrated in rodents to date, while translation ...201931417342
effect of dietary fat and sucrose consumption on cardiac fibrosis in mice and rhesus monkeys.calorie restriction (cr) improved health span in 2 longitudinal studies in nonhuman primates (nhps), yet only the university of wisconsin (uw) study demonstrated an increase in survival in cr monkeys relative to controls; the national institute on aging (nia) study did not. here, analysis of left ventricle samples showed that cr did not reduce cardiac fibrosis relative to controls. however, there was a 5.9-fold increase of total fibrosis in uw hearts, compared with nia hearts. diet composition w ...201931415241
feasibility of hepatitis b vaccination by microneedle patch: cellular and humoral immunity studies in rhesus macaques.this study evaluated dissolvable microneedle patch (dmnp) delivery of hepatitis b vaccine in rhesus macaques and provides evidence that dmnp delivery elicits seroprotective anti-hbs levels comparable with human seroprotection, potentially useful for hepatitis b birth dose vaccination in resource-constrained regions.201931408163
the distribution and nature of responses to broadband sounds associated with pitch in the macaque auditory cortex.the organisation of pitch-perception mechanisms in the primate cortex is controversial, in that divergent results have been obtained, ranging from a single circumscribed 'pitch centre' to systems widely distributed across auditory cortex. possible reasons for such discrepancies include different species, recording techniques, pitch stimuli, sampling of auditory fields, and the neural metrics recorded. in the present study, we sought to bridge some of these divisions by examining activity related ...201931401401
noninvasive spinal neuromodulation to map and augment lower urinary tract function in rhesus macaques.dysfunction of the lower urinary tract (lut) is prevalent in neurological disorders, including multiple sclerosis, stroke, spinal cord injury and neurodegenerative conditions. common symptoms include urgency, incontinence, and urinary retention. recent advances in neuromodulation have resulted in improved treatments for overactive bladder symptoms of urgency, frequency, and nocturia. however, there are presently no treatments available for the induction of voiding to overcome urinary retention. ...201931400304
epigenomic mechanisms of alcohol-induced impaired differentiation of skeletal muscle stem cells; role of class iia histone deacetylases.loss of functional metabolic muscle mass remains a strong and consistent predictor of mortality among people living with human immunodeficiency virus (plwh). plwh have a higher incidence of alcohol use disorder (aud), and myopathy is a significant clinical comorbidity due to aud. one mechanism of skeletal muscle (skm) mass maintenance and repair is by differentiation and fusion of satellite cells (scs) to existing myofibers. previous studies demonstrated that chronic binge alcohol (cba) administ ...201931398085
mechanisms underlying sharpening of visual response dynamics with familiarity.experience-dependent modifications of synaptic connections are thought to change patterns of network activities and stimulus tuning with learning. however, only a few studies explored how synaptic plasticity shapes the response dynamics of cortical circuits. here, we investigated the mechanism underlying sharpening of both stimulus selectivity and response dynamics with familiarity observed in monkey inferotemporal cortex. broadening the distribution of activities and stronger oscillations in th ...201931393260
effect of different anesthetic mixtures-ketamine-xylazine, ketamine-acepromazine and tiletamine-zolazepam-on the physiological and blood biochemistry parameters of male rhesus monkeys (macaca mulatta) at different ages.anesthetic agents are commonly utilized in the handling of non-human primates for prevent the stress caused in physical exploration or physical restrain. for this reason, the objective of this work was to describe the effect of age and dissociative anesthetics (ketamine and tiletamine), and their combinations with acepromazine, xylazine and zolazepam, on the physiological and blood biochemical parameters in macaca mulatta.201931392301
interneuronal correlations at longer time scales predict decision signals for bistable structure-from-motion perception.perceptual decisions are thought to depend on the activation of task-relevant neurons, whose activity is often correlated in time. here, we examined how the temporal structure of shared variability in neuronal firing relates to perceptual choices. we recorded stimulus-selective neurons from visual area v5/mt while two monkeys (macaca mulatta) made perceptual decisions about the rotation direction of structure-from-motion cylinders. interneuronal correlations for a perceptually ambiguous cylinder ...201931391489
strategic deployment of feature-based attentional gain in primate visual cortex.attending to visual stimuli enhances the gain of those neurons in primate visual cortex that preferentially respond to the matching locations and features (on-target gain). although this is well suited to enhance the neuronal representation of attended stimuli, it is nonoptimal under difficult discrimination conditions, as in the presence of similar distractors. in such cases, directing attention to neighboring neuronal populations (off-target gain) has been shown to be the most efficient strate ...201931386656
immune response and reactogenicity of an unadjuvanted intradermally delivered human papillomavirus vaccine using a first generation nanopatch™ in rhesus macaques: an exploratory, pre-clinical feasibility assessment.the human papillomavirus (hpv) 9-valent, recombinant vaccine (gardasil™9) helps protect young adults (males and females) against anogenital cancers and genital warts caused by certain hpv genotypes (ref. gardasil™9 insert). this vaccine is administered intramuscularly (im). the aim of this study was to determine preclinically whether intradermal (id) vaccination with an unadjuvanted 9-valent recombinant hpv vaccine using a first-generation id delivery device, the nanopatch™, could enhance vaccin ...201931384745
pet measures of d1, d2, and dat binding are associated with heightened tactile responsivity in rhesus macaques: implications for sensory processing disorder.sensory processing disorder (spd), a developmental regulatory condition characterized by marked under- or over-responsivity to non-noxious sensory stimulation, is a common but poorly understood disorder that can profoundly affect mood, cognition, social behavior and adaptive life skills. little is known about the etiology and neural underpinnings. clinical research indicates that children with spd show greater prevalence of difficulties in complex cognitive behavior including working memory, beh ...201931379528
molecular cloning, expression and biological activity of rhesus macaque interleukin-17a and interleukin-17f.interleukin-17a (il-17a) and interleukin-17f (il-17f) as two potent proinflammatory cytokines and the signature cytokines of th17 cells play important roles in human autoimmune diseases, inflammation and host defenses. in this study, rhesus macaque il-17a (rhil-17a) and il-17f (rhil-17f) were cloned and expressed, and their biological activities and in vivo distribution were examined. the resulting data showed that both the rhil-17a and rhil-17f genes were consisted of three exons and two intron ...201931377676
long-term tolerance of islet allografts in nonhuman primates induced by apoptotic donor leukocytes.immune tolerance to allografts has been pursued for decades as an important goal in transplantation. administration of apoptotic donor splenocytes effectively induces antigen-specific tolerance to allografts in murine studies. here we show that two peritransplant infusions of apoptotic donor leukocytes under short-term immunotherapy with antagonistic anti-cd40 antibody 2c10r4, rapamycin, soluble tumor necrosis factor receptor and anti-interleukin 6 receptor antibody induce long-term (≥1 year) to ...201931375697
vaccine blunts fentanyl potency in male rhesus monkeys.one proposed factor contributing to the increased frequency of opioid overdose deaths is the emergence of novel synthetic opioids, including illicit fentanyl and fentanyl analogues. a treatment strategy currently under development to address the ongoing opioid crisis is immunopharmacotherapies or opioid-targeted vaccines. the present study determined the effectiveness and selectivity of a fentanyl-tetanus toxoid conjugate vaccine to alter the behavioral effects of fentanyl and a structurally dis ...201931369740
oxytocin and pair compatibility in adult male rhesus macaques (macaca mulatta).pair housing is considered one of the best ways of promoting psychological wellbeing for caged macaques. however, incompatible partnerships can result in stress or aggression. though previous studies have analyzed the role of variables such as age, weight, gender, and temperament on pair compatibility, few have examined the relationship between physiological parameters and pair compatibility. oxytocin is known to promote prosocial nonsexual behavior in various primate species and may serve as an ...201931361040
population variability of rhesus macaque (macaca mulatta) nat1 gene for arylamine n-acetyltransferase 1: functional effects and comparison with human.human nat1 gene for n-acetyltransferase 1 modulates xenobiotic metabolism of arylamine drugs and mutagens. beyond pharmacogenetics, nat1 is also relevant to breast cancer. the population history of human nat1 suggests evolution through purifying selection, but it is unclear whether this pattern is evident in other primate lineages where population studies are scarce. we report nat1 polymorphism in 25 rhesus macaques (macaca mulatta) and describe the haplotypic and functional characteristics of 1 ...201931358821
a computational model of attention control in multi-attribute, context-dependent decision making.real-life decisions often require a comparison of multi-attribute options with various benefits and costs, and the evaluation of each option depends partly on the others in the choice set (i.e., the choice context). although reinforcement learning models have successfully described choice behavior, how to account for multi-attribute information when making a context-dependent decision remains unclear. here we develop a computational model of attention control that includes context effects on mul ...201931354461
mannosylated graphene oxide as macrophage-targeted delivery system for enhanced intracellular m.tuberculosis killing efficiency.tuberculosis (tb), caused by m.tuberculosis (mtb), has become a top killer among infectious diseases. enhancing the ability of anti-tb drugs to kill intracellular mtb in host cells remains a big challenge. here, an innovative nano-system was developed to increase drug delivery and mtb-killing efficacy in mtb-infected macrophages. we employed mannose surface decoration to develop mannosylated and pegylated graphene oxide (go-peg-man). such nano-platform exhibited increased uptake by macrophages v ...201931349400
immunization with pneumocystis recombinant kex1 induces robust and durable humoral responses in immunocompromised non-human primates.infection with the opportunistic fungal pathogen, pneumocystis jirovecii causes life-threatening pneumonia in immunocompromised individuals. in addition to hiv-1 infected patients, individuals at risk of pneumocystis infection include those receiving immunosuppressive therapies due to transplantation, cancer or autoimmune disease. antibiotic treatment is not always successful, and it does not prevent obstructive lung disease after clearance of the pathogen. therefore, it is essential to develop ...201931348719
self-administration of the synthetic cathinones 3,4-methylenedioxypyrovalerone (mdpv) and α-pyrrolidinopentiophenone (α-pvp) in rhesus monkeys.the availability and abuse of synthetic analogues of cathinone have increased dramatically around the world. synthetic cathinones, such as 3,4-methylenedioxypyrovalerone [mdpv] and α-pyrrolidinopentiophenone [α-pvp], are cocaine-like inhibitors of monoamine transporters and common constituents of "bath salts" or "flakka" preparations. studies in rats suggest that mdpv and α-pvp are 3 to 4-fold more effective reinforcers than cocaine; however, comparisons of the relative reinforcing effectiveness ...201931346629
effects of methamphetamine isomers on d-methamphetamine self-administration and food-maintained responding in male rats.methamphetamine (meth) abuse is generally attributed to the d-isomer. self-administration of l-meth has been examined only in rhesus monkeys with a history of cocaine self-administration or drug-naïve rats using high toxic doses.201931346628
primate prefrontal neurons signal economic risk derived from the statistics of recent reward experience.risk derives from the variation of rewards and governs economic decisions, yet how the brain calculates risk from the frequency of experienced events, rather than from explicit risk-descriptive cues, remains unclear. here, we investigated whether neurons in dorsolateral prefrontal cortex process risk derived from reward experience. monkeys performed in a probabilistic choice task in which the statistical variance of experienced rewards evolved continually. during these choices, prefrontal neuron ...201931343407
aav-delivered ecd4-ig protects rhesus macaques from high-dose sivmac239 challenges.a number of simian and simian human immunodeficiency viruses (siv and shiv, respectively) have been used to assess the efficacy of hiv-1 vaccine strategies. among these, sivmac239 is considered among the most stringent because, unlike shiv models, its full genome has coevolved in its macaque host and its tier 3 envelope glycoprotein (env) is exceptionally hard to neutralize. here, we investigated the ability of ecd4-ig, an antibody-like entry inhibitor that emulates the hiv-1 and siv receptor an ...201931341061
human immunodeficiency virus c.1086 envelope gp140 protein boosts following dna/modified vaccinia virus ankara vaccination fail to enhance heterologous anti-v1v2 antibody response and protection against clade c simian-human immunodeficiency virus challenge.the rv144 human immunodeficiency virus type 1 (hiv-1) vaccine trial showed a strong association between anti-gp70 v1v2 scaffold (v1v2) and anti-v2 hot spot peptide (v2 hs) antibody responses and reduced risk of hiv infection. accordingly, a primary goal for hiv vaccines is to enhance the magnitude and breadth of v1v2 and v2 hs antibody responses in addition to neutralizing antibodies. here, we tested the immunogenicity and efficacy of hiv-1 c.1086 gp140 boosts administered sequentially after pri ...201931341049
chimpanzee adenoviral vector prime-boost regimen elicits potent immune responses against ebola virus in mice and rhesus macaques.in the last few decades, ebola virus (ebov) has emerged periodically and infected people in africa, resulting in an extremely high mortality rate. with no available prophylaxis or cure so far, a highly effective ebola vaccine is urgently needed. in this study, we developed a novel chimpanzee adenovirus-based prime-boost vaccine by exploiting two recombinant replication-deficient chimpanzee adenoviral vectors, adc7 and adc68, which express glycoproteins (gp) of the ebov strain identified in the 2 ...201931339465
re-analysis of data reveals no evidence for neonatal imitation in rhesus macaques.over the past decade, a growing number of publications have claimed to provide evidence for the existence and function of neonatal imitation in rhesus macaques. here i show that there is in fact no empirical basis for these claims. studies of the phenomenon have consistently failed to implement the gold standard cross-target analytical approach, which controls for increases in matching responses that may not be a function of the specific modelled behaviour. critically, a pre-registered re-analys ...201931337292
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